Antihistamine composition

ABSTRACT

An extraction process and composition produced thereby for use as an antihistamine is disclosed. The composition comprises an extraction of  Loranthus , which is derived from a species of  Loranthus  known to possess quantities of quercetin and avicularin, which may be administered orally in an amount up to 300 mg per day, and preferably between 100 to 300 mg per day. The extraction process comprises forming an ethanol extraction from raw  Loranthus , filtering the extract, and passing the filtered product through a separation column, eluting, distilling and concentrating the resultant extract and thereafter applying a vacuum to remove water and solvents to produce a concentrated powdered form of the extract.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional application of U.S. patentapplication Ser. No. 10/692,423, filed Oct. 23, 2003 and issued as U.S.Pat. No. 6,896,913, which was a continuation-in-part of U.S. patentapplication Ser. No. 10/161,936, filed Jun. 4, 2002, now abandoned.

STATEMENT RE: FEDERALLY SPONSORED RESEARCH/DEVELOPMENT

Not Applicable

BACKGROUND OF THE INVENTION

The present invention is directed to extraction processes andcompositions produced thereby that are useful as antihistamines to treatallergies and hypersensitivity reactions.

In this regard, allergic or hypersensitivity reactions and the use ofantihistamines to treat the same are well-known. Generally, such areaction is initiated by an allergen, such as a dust particle, drug,food or plant pollen, for example, that acts as an antigen to stimulatean immune response when encountered by the body. During such an event,antibodies of the immunoglobulin E(IgE) class bind with mast cells intissues that ultimately causes histamine to be released. Typically, suchallergic reactions tend to be mild and consist of primarily of watery,itchy eyes accompanied by some sneezing. Some allergic reactions,however, can be moderate to severe, and even life threatening in thecase of anaphylaxis.

Most allergies are treated by the use of antihistamines, which block thehistamine1 receptor. A wide variety of prescription and nonprescriptionantihistamines are currently available, and include promethazine,loratadine, and fexofenadine, which are available by prescription, anddiphenhydramine triprolidine, and pyrilamine, which are available overthe counter. Generally, such antihistamines are useful in treatingallergy symptoms, and in particular seasonal hay fever, allergicrhinitis and conjunctivitis.

All such antihistamines, however, can produce undesired or adverseeffects. In this regard, most antihistamines tend to cause drowsiness,and can further cause confusion, light-headedness, dry mouth,constipation, difficulty with urination, and blurred vision. These sideeffects can be especially pronounced in the elderly or in individualsthat have developed sensitivities to such drugs. While advances havebeen made to minimize some of the side effects, such as the developmentof nonsedating antihistamines such as loratadine and fexofenadine, thesame still pose substantial risks when administered to certainindividuals.

As such, there is a substantial need in the art for antihistaminecompositions and methods of making the same that are therapeuticallyeffective in treating allergic actions, as per conventionalantihistamines, but do not produce many of the adverse side effectstypically associated with antihistamines. There is a further need in theart for such compositions and methods for making the same that arederived from natural plant materials that can be produced via extractionprocesses, as opposed to conventional pharmaceutical and chemicalmanufacturing techniques. There is a further need in the art for such acomposition and method of making of the same that are of relatively lowcost, substantially easier to produce and practice, and, with respect tothe antihistamine composition, are far safer and capable of beingutilized in far greater patient populations than conventionalantihistamine remedies.

BRIEF SUMMARY OF THE INVENTION

The present invention specifically addresses and alleviates theabove-identified deficiencies in the art. In this regard, the presentinvention is directed to an extraction process and composition producedthereby that is safe and effective for use as an antihistamine. Thecomposition comprises a purified extract of Loranthus selected from aspecies known to possess quercetin and avicularin, two well-knownflavinoids in the art, that can be extracted therefrom. Exemplary ofsuch species include Loranthus parasiticus (l.) Merr and Loranthuschinesis. The composition may be administered orally and, for humansubjects, may be administered in a single daily dose of 300 mg.Preferably, such daily oral dose will be between 100 and 300 mg.

The extract is derived through a novel extraction process whereby rawflavinoid-containing Loranthus is harvested, dried and crushed such thatthe same preferably has a particulate size capable of passing through40-mesh U.S. Series sieve. An ethanol solution, which is preferably 95%food grade ethanol, is added in amount of approximately five times theweight of the crushed Loranthus material to form a first admixture. Thefirst admixture is placed within an extraction pot that is heated to nogreater than 80° C. and allowed to reflux for approximately one to twohours. To further enhance the recovery of the extract, an additionalamount of 95% ethanol solution may be added to the heated admixture withthe resultant admixture again being reheated for up to an addition oneto two hours.

The heated admixture is allowed to cool and filtered such that anyresidue is removed to thus produce a filtrate solution. Such filteringprocess is conducted until such time as the filtered solution possessesa density of 0.9 grams per cubic centimeter (g/cm3) or less andpreferably between 0.8 gm/cm3 to 0.9 gm/cm3. The filtrate solution isthen steam heated until the same possesses a creamy consistency and maybe either dried and crushed such that the same takes the form of apowder for future use, or may be mixed with distilled water to producethe final extract. In either case, whether it be the cream derivative orpowderized form thereof, the same is mixed with distilled water suchthat a resultant solution is produced which is approximately 15–20% byweight steam heated cream or powdered derivative thereof and 80–85%distilled water. Such solution is then passed through a filtrationmembrane, which is preferably 100 screen mesh, with the filtratesolution then being purified via passage through a chromatographiccolumn utilizing XAD®-2 resin or any suitable equivalent thereof.

Once the filtrate solution is introduced into the column, distilledwater is then passed through the column in an amount of approximatelythree times the volume of the filtrate solution (i.e., the amountintroduced into the column). The distilled water is allowed to passthrough the column and discarded. Following the washing of the resinwith the distilled water, the column is then eluted with an ethanolsolution, which is preferably approximately 50% food-grade ethanol, inan amount of approximately three to five times the volume of the column.The eluate is then collected, distilled, and concentrated until a finalcream-like isolate is produced. Such isolate is then vacuum dried andcrushed to a powder, which may then be packaged and then administeredfor use as an antihistamine.

BRIEF DESCRIPTION OF THE DRAWINGS

These as well as other features of the present invention will becomemore apparent upon reference to the drawings wherein:

FIG. 1 is a flow chart depicting the steps to utilized to perform anextraction procedure in accordance with the preferred embodiment of thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

The detailed description set forth below is intended as a description ofthe presently preferred embodiment of the invention, and is not intendedto represent the only form in which the present invention may beconstructed or utilized. The description sets forth the functions andsequences of steps for constructing and operating the invention. It isto be understood, however, that the same or equivalent functions andsequences may be accomplished by different embodiments and that they arealso intended to be encompassed within the scope of the invention.

Referring now to FIG. 1, there is depicted a flow chart illustrating aprocess 10 for producing an extract of Loranthus that is useful as asafe and effective antihistamine, which has substantially fewer sideeffects than conventional antihistamines and further, is derived fromall-natural plant products.

In the initial step 20, raw materials, namely, harvested Loranthusplants are provided. Although a wide variety of species of Loranthus areknown, for purposes of practicing the present invention only thosespecies of Loranthus should be utilized that are known to possess highconcentrations of the flavinoids quercetin and avicularin. In preferredembodiments of the present invention, Loranthus chinesis and Loranthusparasiticus (l.) Merr plants are utilized. Such plants are well-knownand are extensively planted in southern China. Such plants are typicallycharacterized by short growing stems that are from 1–2 mm and have adiameter of typically between 0.2 to 0.8 mm. Such plants may further becharacterized by leaves having a taupe to mahogany-type color. Prior touse, the materials are preferably dehydrated or otherwise dried.

Such raw materials 20 are then crushed in step 30 into particles thatare preferably capable of passing through a 40-mesh US Series sieve. Asis well-known, such mesh size is known in the art and are defined by thenumber of openings per unit area.

Once sufficiently crushed, an ethanol extraction 40 is performed wherebythe crushed raw materials are mixed with a solution of approximately 95%ethanol such that the ratio of ethanol solution to crushed products isapproximately 5:1 by weight. As will be appreciated by those skilled inthe art, the ethanol solution will, comprise food-grade ethanol, whichis commercially available from a variety, of manufacturers. Theadmixture of ethanol with crushed raw material is heated and allowed toreflux for approximately one to two hours at a temperature not to exceed80° C. Preferably, such ethanol extraction is performed at approximately78–80° C. To conduct such step, the same may be utilized in aconventional stainless steel extraction pot with reflux system. As anoptional additional step, the ethanol extraction 40 may include addingadditional amounts of ethanol (i.e. 95% ethanol solution) in amounts upto the original amount added; namely, approximately five times theweight of the crushed Loranthus parasfticus (l.) Merr and the resultantadmixture again heated up to 80° C. for up to an additional two hours.

The resultant ethanol admixture is then allowed to cool and thenconcentrated in step 50 by filtering off any residue present in theadmixture. To that end, the residue may be removed via conventionalfiltering techniques, such as skimming and the like, and is conducteduntil the solution possesses a density up to 0.9 gm/cm3 and preferablybetween 0.8 gm/cm3 to 0.9 gm/cm3. The removed residue may be discarded.The concentrated solution, on the other hand, is steam heated to enablethe same to undergo a rough cream extraction, in next step 50. To thatend, the concentrated solution is heated and steamed, preferably via theuse of a jacketed kettle, until the solution transforms into a creamyresidue. In this respect, such procedure may be performed viaconventional ethanol extraction processes known in the art.

Once the cream has been generated through the steam heating, the same isremoved and further processed via next step 60. As an alternative, thecream extracted via step 50 may be dried via conventional dryingtechniques, for example vacuum drying, such that the same transitionsinto a powder which may be stored and processed further at a later timeas per the cream extracted through the rough cream extraction 50discussed below.

In either case, whether it be the cream directly extracted from therough cream extraction 50 or the powdered form derived therefrom, thesame is dissolved with distilled water via step 60. In such step,distilled water is mixed with the cream extract or powdered form thereofsuch that a solution or admixture is produced which is approximately15–20% by weight cream extract (or powder thereof) and 80–85% by weightdistilled water. Once produced, the same is filtered via step 70. Tothat end, the solution/admixture is preferably passed through afiltration membrane, which preferably comprises a 100 screen mesh, withthe filtrate being collected thereafter. Any residue not passing suchscreen mesh is discarded.

Such filtrate is then purified in step 80 by passing the same through achromatography column in order to separate and isolate the sought afterextract. To achieve such result, conventional chromatographic techniquesmay be utilized. According to a preferred embodiment, conventionalchromatographic columns using XAD®-2 type media or resin may beutilized. As is well-known in the art, XAD®-2 resin produced by Rohm andHaas, of Philadelphia, Pa. is widely known and commercially available.It should be recognized, too, that any equivalent of such resin, such asUltra-Clean™ resin produced by Restek Corporation of Bellefonte, Pa. maybe utilized. Such columns with resin utilized therewith are prepared asper conventional techniques with the filtrate produced in step 70 beingadministered thereto as per conventional chromatographic columnseparation practices.

In this respect, the filtrate is administered through the top of theprepared column, followed by the passing of distilled water through thecolumn in an amount of approximately 3 times the amount of the filtrateintroduced therewithin. For example, to the extent that one liter offiltrate is administered to the column, three liters of distilled waterwill be passed through the column thereafter. Such distilled water isdiscarded once it has been passed through the chromatography column.

Following the distilled water wash of the column, the column is elutedwith an approximately 50% ethanol solution of food-grade quality.Preferably, such solution is passed through the column in a volumeranging between approximately 3–5 times the volume of the chromatographycolumn with the eluate being collected as the same is passed through thecolumn. Once the eluate has been collected, the chromatographic columnmay then be rinsed with 95% ethanol solution followed by distilled waterand utilized for future applications.

With respect to the ethanol eluate, the same is distilled andconcentrated until a further creamy residue is isolated, as per step110. Prior to concentrating, an optional test procedure 100 may beperformed whereby the purified extract is compared against extractsamples of known purity. In one preferred test, the extract is testedvia thin layer chromatography wherein a portion of the extract purifiedin step 80 is mixed with a developing agent comprising a mix solution ofchloroform, methanol and water being mixed in a ration of approximately3:1:0.2 by weight. Preferably, such developing agent is mixed with thesample and allowed to stand for 12 hours until a bottom layer of solventis formed. Such a bottom layer of solvent may be tested against knownstandards utilizing known thin layer chromatography techniques to insuresample purity and concentration.

Whether or not the same is tested for purity, the creamy residueproduced in step 11 is then vacuum dried, via drying step 120, andthereafter crushed in step 130 to thus generate a powder of extraction,which is obtained in step 140. Such extraction powder may then bepackaged in step 150 as per any of a variety of conventionalpharmaceutical packaging techniques.

Along these lines, it is contemplated that such extraction powder may bemixed with a variety of pharmaceutically acceptable carriers and inertingredients, such as cellulose and the like, for shipping anddistribution. Additionally, such powdered form of the extract isbelieved to be capable of being integrated into food products, suchfruit and grain based snack foods, beverages, such as fortified fruitdrinks, confectioneries, candy, and the like to thus provide alternativemethods of administrating such product. To the extent such extractionremains in its raw form, however, it is believed that the same should bestored away from heat sources, and also should be kept in low-humiditycontainers is so far as such extraction powder has been shown to readilydissolve in water. Accordingly, conventional packaging practices shouldbe followed with respect to the storage and handling of such extractionpowder.

As an illustration, two (2) non-restrictive examples of methods ofpracticing the extraction process of the present invention are givenbelow.

EXAMPLE ONE

Approximately 5000 grams of Loranthus parasiticus (l.) Merr is crushedand placed in an extraction pot with 15 liters of a 95% ethanol solutionand heated until such temperature reached 78° C. and thereafter allowedto reflux for approximately 1.5 hours. Plant residue was removed byfiltration and the resultant mixture was combined with an additional tenliters of 95% ethanol solution. The resultant admixture was then heatedto approximately 80° C. and allowed to reflux for approximately onehour. The ethanol solution was filtered again such that the concentratepossessed a solution density of 0.8 grams per cubic centimeter wasattained.

Such filtrate was then mixed with distilled water such that a solutionwas produced of approximately 20% by weight of the filtrate and 80% byweight of distilled water. Such solution was filtered and passed througha chromatography column utilizing the equivalent of XAD®-2 resin. Thecolumn was washed with five liters of distilled water and elutedthereafter with 50% ethanol. The resultant extract was collected andconcentrated, via distillation, until the same became a cream isolate,which was dried further into powdered form. Such procedure generatedapproximately 150 grams of the Loranthus parasiticus(l.) Merr extract.

EXAMPLE TWO

Approximately 10 kg of Loranthus parasiticus (l.) Merr was crushed andplaced in an extraction pot with 25 liters of 95% ethanol solution andheated to approximately 80 Nc and allowed to reflux for approximatelytwo hours. The reflux solution was filtered and mixed with an additional25 liters of 95% ethanol solution, which was then refluxed further atapproximately 80 Nc for approximately two hours. The resultant admixturewas filtered such that the concentrate possessed a density of 0.9 gramsper cubic centimeter.

The filtrate was then mixed with distilled water such that a solutionwas produced whereby the same was approximately 15% by weight filtrateand 85% by weight distilled water. Such solution was then passed througha chromatography column utilizing a chromatographic resin equivalent toXAD®-2 followed by the administration of 10 liters of distilled water,which was passed through the chromatography column and discarded. Thecolumn was then eluted with a 50% ethanol solution, with the eluatecollected and concentrated until the Loranthus parasiticus (l.) Merrcream extract was isolated. The same was then vacuum dried into powderform. Via such procedure, approximately 220 grams of the Loranthusparasiticus (l.) Merr extraction was derived.

Irrespective of the form by which the final extract produced by theforegoing process takes and is administered, the same exhibits superiorproperties as an antihistamine. For human subjects, it is believed thatadministering the powder extract derived from the process of the presentinvention in an amount of up to 300 mg in a single oral dose will besufficient to treat most allergies and allergic reactions. In apreferred embodiment, a single oral dosage of approximately 100 to 300mg in one daily oral dose it is believed sufficient to treat mostallergic or hypersensitivity reactions in human subjects.

As discussed above, such oral dose may be administered via of a varietyof formulations known in the art, including tablets, capsules,suspensions, or by the addition of such extract as part of a foodproduct or beverage, such as fruit-based in grain-based snack foods,such as cereal bars and the like, fortified fruit beverages, and otherfortified foods, candy and confectionaries. Advantageously, the extractof the present invention has been shown to produce little, if any, sideeffects typically associated with antihistamines, and further,exclusively comprises a plant derivative which omits any type of rawchemical processing as do virtually all type of antihistamines currentlyavailable.

With respect to the mode of action, it is currently believed that theLoranthus extract derived through the methods of the present inventioncontain high concentrations of flavonoids, and in particular quercetinand avicularin, which are believed to possess potent antihistamine andanti-inflammatory properties. It is further believed that suchcompositions possess antioxident properties as well, and may furtherprovide substantial therapeutic benefit in that regard. Accordingly, theprocess of the present invention and composition produced thereby arebelieved to possess substantial benefits and therapeutic properties thatare readily suited to enhance health and wellness.

As will be appreciated, additional modifications and improvements of thepresent invention may also be apparent to those of ordinary skill in theart. Thus, the particular combination of parts and steps described andillustrated herein is intended to represent only certain embodiments ofthe present invention, and is not intended to serve as limitations ofalternative devices and methods within the spirit and scope of theinvention.

1. A method for treating an allergic reaction in a human subject, saidmethod comprising the step: a) administering an ethanol extract ofLoranthus in a therapeutic amount to said human subject.
 2. The methodof claim 1 wherein said extract is administered orally in an amount upto 300 mg.
 3. The method of claim 2 wherein said extract is administeredin an amount between approximately 100 mg to 300 mg.
 4. The method ofclaim 1 wherein said extract is administered as part of a food product.5. The method of claim 4 wherein said food product is selected from thegroup consisting of fruit-based snack products, grain-based, snackproducts, fortified fruit drinks, fortified dairy products, candy andconfectionaries.
 6. The method of claim 1 wherein said extract ofLoranthus is derived from a species of Loranthus selected from the groupconsisting of Loranthus parasiticus (l.) Merr and Loranthus chinesis.